Functional Implications of the IL-6 Signaling Pathway in Keloid Pathogenesis

Ghazizadeh, Mohammad; Tosa, Mamiko; Shimizu, Hajime; Hyakusoku, Hiko; Kawanami, Oichi

doi:10.1038/sj.jid.5700564

Cited by 147 publications

(147 citation statements)

References 43 publications

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“…[5][6][7][8][9][10][11][12] Modifications in growth factor-regulated cell growth and apoptosis, intracellular signal transduction, and epidermis-dermis interactions have been reported. [13][14][15][16][17][18][19][20][21] Changes in the level of genes involved in the above phenomena were also detected in gene profiling studies. 22,23 Despite these findings, knowledge-based specific approaches for prevention and efficacious treatment of keloids are still absent, and the lack of proper in vitro and animal models that recapitulate the pathophysiology of keloids further hampers progress.…”

mentioning

confidence: 99%

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Tuan

Hwu

et al. 2008

The American Journal of Pathology

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Keloids are tumor-like skin scars that grow as a result of the aberrant healing of skin injuries, with no effective treatment. We provide new evidence that both overexpression of plasminogen activator inhibitor-1 (PAI-1) and elevated collagen accumulation are intrinsic features of keloid fibroblasts and that these characteristics are causally linked. Using seven strains each of early passage normal and keloid fibroblasts, the keloid strains exhibited inherently elevated collagen accumulation and PAI-1 expression in serumfree, 0.1% ITS؉ culture; larger increases in these parameters occurred when cells were cultured in 3% serum. To demonstrate a causal relationship between PAI-1 overexpression and collagen accumulation, normal fibroblasts were infected with PAI-1-expressing adenovirus. Such cells exhibited a two-to fourfold increase in the accumulation of newly synthesized collagen in a viral dose-dependent fashion in both monolayers and fibrin gel, provisional matrix-like cultures. Three different PAI-1-targeted small interfering RNAs, alone or in combination, produced greater than an 80% PAI-1 knockdown and reduced collagen accumulation in PAI-1-overexpressing normal or keloid fibroblasts. A vitronectin-binding mutant of PAI-1 was equipotent with wild-type PAI-1 in inducing collagen accumulation, whereas a complete protease inhibitor mutant retained approximately 50% activity. Thus, PAI-1 may use more than its protease inhibitory activity to control keloid collagen accumulation. PAI-1-targeted interventions , such as small interfering RNA and lentiviral short hairpin RNA-containing microRNA sequence suppression reported here , may have therapeutic utility in the prevention of keloid scarring.

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mentioning

confidence: 99%

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Tuan

Hwu

et al. 2008

The American Journal of Pathology

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“…Il6 activity has also been implicated in keloid formation. 32 In the inflammation category, we identified 25 genes with a 4-fold increase in the thermal stress areas and eight genes that showed a 4-fold, or greater, decrease in expression. These results are shown in Table 4.…”

Section: Discussionmentioning

confidence: 99%

Image-guided genomic analysis of tissue response to laser-induced thermal stress

et al. 2011

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Abstract. The cytoprotective response to thermal injury is characterized by transcriptional activation of "heat shock proteins" (hsp) and proinflammatory proteins. Expression of these proteins may predict cellular survival. Microarray analyses were performed to identify spatially distinct gene expression patterns responding to thermal injury. Laser injury zones were identified by expression of a transgene reporter comprised of the 70 kD hsp gene and the firefly luciferase coding sequence. Zones included the laser spot, the surrounding region where hsp70-luc expression was increased, and a region adjacent to the surrounding region. A total of 145 genes were up-regulated in the laser irradiated region, while 69 were up-regulated in the adjacent region. At 7 hours the chemokine Cxcl3 was the highest expressed gene in the laser spot (24 fold) and adjacent region (32 fold). Chemokines were the most common up-regulated genes identified. Microarray gene expression was successfully validated using qRT-polymerase chain reaction for selected genes of interest. The early response genes are likely involved in cytoprotection and initiation of the healing response. Their regulatory elements will benefit creating the next generation reporter mice and controlling expression of therapeutic proteins. The identified genes serve as drug development targets that may prevent acute tissue damage and accelerate healing. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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“…Ostatnio postuluje się, że IL-6 odgrywa kluczową rolę w tego typu procesach, dlatego hamowanie tej cytokiny może stanowić obiecujący cel terapeutyczny w zapobieganiu powstawaniu blizn [23,24]. Terapia światłem LED obniża poziom mRNA IL-6, co w konsekwencji może przeciwdziałać bliznowaceniu miejsc poddanych zabiegom, po urazach czy w trądziku [4,25].…”

Section: Przerosłe Blizny I Keloidyunclassified

Effects of LED radiation on the skin – what is new in recent research? Part II. In skin remodeling processes and hair growth

Dana¹,

Batory²,

Erkiert‐Polguj³

et al. 2015

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Przegląd Dermatologiczny 2015/6 564 STRESZCZENIE Światło LED (ang. light emitting diodes) znalazło szerokie zastosowanie w medycynie estetycznej i kosmetologii, głównie ze względu na moż-liwości pobudzania przebudowy skóry właściwej bez wywoływania efektu termicznego. Szczególne znaczenie ma to w planowaniu terapii przeciwstarzeniowych oraz gojeniu ran. Okazało się, że światło LED stymuluje proliferację fibroblastów, syntezę kolagenu, czynników wzrostu, wytwarzanie macierzy zewnątrzkomórkowej oraz pobudza mikrokrążenie skóry (stosowano różne długości fali światła: 590 nm, 630 nm, 633 nm, 830 nm). Ponadto w badaniach na myszach stwierdzono wpływ zielonego światła LED (518 nm) na przyspieszenie gojenia ran. Terapia ta może również przeciwdziałać bliznowaceniu. Ciekawym aspektem oddziaływania światła LED jest także pobudzanie wzrostu włosów (638 nm). ABSTRACTLight-emitting diodes (LED) have found widespread use in aesthetic medicine and cosmetology, mainly due to the possibility to stimulate the dermis without inducing a thermal effect. This is of particular importance in planning anti-aging therapies and wound healing. LED light stimulates fibroblast proliferation, collagen synthesis, growth factors, extracellular matrix production and skin microcirculation (used as different wavelengths of light: 590 nm, 630 nm, 633 nm, 830 nm). Furthermore, experiments with mice have shown the effectiveness of green waves (518 nm) in wound healing. This therapy can also prevent scarring. The impact of red waves (638 nm) is also interesting -they accelerate the rate of hair regrowth.Oddziaływanie światła LED na skórę -co nowego w badaniach z ostatnich lat? Część II: W procesach przebudowy skóry oraz wzroście włosów

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Functional Implications of the IL-6 Signaling Pathway in Keloid Pathogenesis

Cited by 147 publications

References 43 publications

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Image-guided genomic analysis of tissue response to laser-induced thermal stress

Effects of LED radiation on the skin – what is new in recent research? Part II. In skin remodeling processes and hair growth

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